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The Role of IL-33/ST2 Pathway in Tumorigenesis

Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
Department of Biological Sciences and Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA
Author to whom correspondence should be addressed.
Present address: Department of Pathology, Brown University, Providence, RI 02912, USA.
Present address: Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, Maharashtra, India.
Int. J. Mol. Sci. 2018, 19(9), 2676;
Received: 26 April 2018 / Revised: 5 September 2018 / Accepted: 6 September 2018 / Published: 9 September 2018
(This article belongs to the Special Issue Tumor Microenvironment)
Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane of target cells to potently activate a T Helper 2 (Th2) immune response, thus, it is classified as an alarmin. While its role in immunity and immune-related disorders has been extensively studied, its role in tumorigenesis is only beginning to be elucidated and has revealed opposing roles in tumor development. The IL-33/ST2 axis is emerging as a potent modulator of the TME. By recruiting a cohort of immune cells, it can remodel the TME to promote malignancy or impose tumor regression. Here, we review its multiple functions in various cancers to better understand its potential as a therapeutic target to block tumor progression or as adjuvant therapy to enhance the efficacy of anticancer immunotherapies. View Full-Text
Keywords: Interleukin 33; IL-33/ST2 signaling; tumor microenvironment; inflammation; cancer Interleukin 33; IL-33/ST2 signaling; tumor microenvironment; inflammation; cancer
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MDPI and ACS Style

Larsen, K.M.; Minaya, M.K.; Vaish, V.; Peña, M.M.O. The Role of IL-33/ST2 Pathway in Tumorigenesis. Int. J. Mol. Sci. 2018, 19, 2676.

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